Toxicology and human health risk assessment of polyethoxylated tallow amine surfactant used in glyphosate formulations.

Roundup® branded herbicides contain glyphosate, a surfactant system and water. One of the surfactants used is polyethoxylated tallow amine (POE-T). A toxicology dataset has been developed to derive the most representative points of departure for human health risk assessments. Concentrated POE-T was very irritating to skin, corrosive to eyes, and sensitizing to skin. The irritation and sensitization potential of POE-T diminishes significantly upon dilution with water. Repeated dosing of rats with POE-T produced gastrointestinal effects but no systemic effect on organ systems. POE-T was not genotoxic and had no effect on embryo-fetal development or reproduction. The occupational risk assessment of POE- T for the agricultural use of glyphosate products has demonstrated that margins of exposure (MOEs) are 2517 and 100,000 for maximum and geometric mean dermal exposures, respectively. In the food risk assessment for relevant agricultural uses, the range of MOEs for consumption of foods from plant and animal origin were 330 to 2909. MOEs ≥100 are generally considered to be of no toxicological concern. Based on the results of the occupational and food risk assessments, it is concluded that there are no significant human health issues associated with the use of POE-T as a surfactant in glyphosate products.

Ordered mesoporous silica to enhance the bioavailability of poorly water-soluble drugs: Proof of concept in man.

Formulating poorly water soluble drugs using ordered mesoporous silica materials is an emerging approach to tackle solubility-related bioavailability problems. The current study was conducted to assess the bioavailability-enhancing potential of ordered mesoporous silica in man. In this open-label, randomized, two-way cross-over study, 12 overnight fasted healthy volunteers received a single dose of fenofibrate formulated with ordered mesoporous silica or a marketed product based on micronized fenofibrate. Plasma concentrations of fenofibric acid, the pharmacologically active metabolite of fenofibrate, were monitored up to 96h post-dose. The rate (Cmax/dose increased by 77%; tmax reduced by 0.75h) and extent of absorption (AUC0-24h/dose increased by 54%) of fenofibrate were significantly enhanced following administration of the ordered mesoporous silica based formulation. The results of this study serve as a proof of concept in man for this novel formulation approach.

Genotoxic potential of glyphosate formulations: mode-of-action investigations.

A broad array of in vitro and in vivo assays has consistently demonstrated that glyphosate and glyphosate-containing herbicide formulations (GCHF) are not genotoxic. Occasionally, however, related and contradictory data are reported, including findings of mouse liver and kidney DNA adducts and damage following intraperitoneal (ip) injection. Mode-of-action investigations were therefore undertaken to determine the significance of these contradictory data while concurrently comparing results from ip and oral exposures. Exposure by ip injection indeed produced marked hepatic and renal toxicity, but oral administration did not. The results suggest that ip injection of GCHF may induce secondary effects mediated by local toxicity rather than genotoxicity. Furthermore, these results continue to support the conclusion that glyphosate and GCHF are not genotoxic under exposure conditions that are relevant to animals and humans.

A review of the genotoxicity of triallate.

Triallate is a selective herbicidal chemical used for control of wild oats in wheat. It has an extensive genotoxicity database that includes a variety of in vitro and in vivo studies. The chemical has produced mixed results in in vitro assay systems. It was genotoxic in bacterial mutation Ames assays, predominantly in Salmonella typhimurium strains TA100 and TA1535 in the presence of S9. Weaker responses have been observed in TA100 and TA1535 in the absence of S9. Mixed results have been observed in strain TA98, whereas no genotoxicity has been observed in strains TA1537 and TA1538. The presence and absence of S9 and its source seem to play a role in the bacterial response to the chemical. There have also been conflicting results in other test systems using other bacterial genera, yeast, and mammalian cells. Chromosome effects assays (sister-chromatid exchange and cytogenetics assays) have produced mixed results with S9 but no genotoxicity without S9. Triallate has not produced any genotoxicity in in vitro DNA damage or unscheduled DNA synthesis assays using EUE cells, human lymphocytes, and rat and mouse hepatocytes. In a series of in vivo genotoxicity assays (cytogenetics, micronucleus, dominant lethal, and unscheduled DNA synthesis), there has been no indication of any adverse genotoxic effect. Metabolism data indicate that the probable explanation for the differences observed between the in vitro studies with S9 and without S9 and between the in vitro and the in vivo studies is the production of a mutagenic intermediate in vitro at high doses of triallate is expected to be at most only transiently present in in vivo studies. The weight of evidence strongly suggests that triallate is not likely to exert mutagenic activity in vivo due to toxicokinetics and metabolic processes leading to detoxification.